Short chain fatty acids (SCFAs) produced by gut microbiota are known to play primary roles in gut homeostasis by immunomodulation partially through G-protein coupled receptors (GPR) 43. Using mouse models of TLR ligand induced keratitis, we investigated whether SCFAs and GPR43 play any regulatory roles in the pathogenesis of inflammatory responses in the eye. Both human and mouse eyes were labeled with a specific antibody for GPR43 and imaged by a laser scanning confocal microscope. Corneal cups from naïve C57BL/6J (B6) and GPR43 knockout (KO) mice were stimulated with TLR ligands in the presence or absence of sodium butyrate overnight and then processed for RT-PCR assay for expression of GPR43 and cytokines. Keratitis was induced by Poly I:C in wild type (WT) B6, GPR43KO and chimeric mice and the disease severity was evaluated by the corneal fluorescein staining test, and infiltrating cell staining and calculating in corneal whole mount. GPR43 is expressed in both human and mouse eyes and the expression is bidirectionally regulated by TLR ligands and butyrate. Butyrate significantly inhibited inflammation caused by several TLR ligands such as Poly I:C, Flagellin, and CpG-ODN (TLR-3, 5 and 9 agonists, respectively) in WT, but not GPR43KO, mice. Butyrate inhibition of TLR-induced keratitis is mediated by the GPR43 expressed in tissue but not hematopoietic, cells. This is the first report to demonstrate of the protective effect of SCFAs on microbial keratitis, and the dynamic expression and anti-inflammatory function of GPR43 in the eye. SCFAs can modulate inflammation and immunity in the eye through GPR43.

中文翻译：

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短链脂肪酸通过眼 G 蛋白偶联受体抑制角膜对 TLR 配体的炎症反应 43

目的

已知肠道微生物群产生的短链脂肪酸 (SCFA)在肠道稳态中发挥主要作用，部分通过 G 蛋白偶联受体 (GPR) 43 进行免疫调节。使用TLR 配体诱导的角膜炎小鼠模型，我们研究了 SCFA 和 GPR43 是否发挥作用眼睛炎症反应发病机制中的任何调节作用。

方法

人和小鼠的眼睛都用 GPR43 特异性抗体标记，并通过激光扫描共聚焦显微镜成像。在存在或不存在丁酸钠的情况下，用 TLR 配体刺激来自幼稚 C57BL/6J (B6) 和 GPR43 敲除 (KO) 小鼠的角膜杯过夜，然后进行 RT-PCR 测定以检测 GPR43 和细胞因子的表达。在野生型（WT）B6、GPR43KO和嵌合小鼠中采用Poly I:C诱导角膜炎，并通过角膜荧光素染色试验、角膜全片浸润细胞染色和计算来评估疾病严重程度。

结果

GPR43 在人和小鼠眼中都有表达，并且表达受到 TLR 配体和丁酸盐的双向调节。丁酸盐可显着抑制 WT 小鼠中由多种 TLR 配体（例如 Poly I:C、鞭毛蛋白和 CpG-ODN（分别为 TLR-3、5 和 9 激动剂））引起的炎症，但不能抑制 GPR43KO 小鼠。TLR 诱导的角膜炎的丁酸盐抑制作用是由组织中表达的 GPR43 介导的，但造血细胞中不表达。

结论

这是第一份证明SCFA对微生物性角膜炎的保护作用以及GPR43在眼中的动态表达和抗炎功能的报告。SCFA 可以通过 GPR43 调节眼部炎症和免疫。